Is DLX3 p.Ser212= (c.636A>G) pathogenic?

DLX3 p.Ser212= (c.636A>G) is classified Likely benign in DLX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0165%, sas); Associated with hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism.

What condition is associated with DLX3 p.Ser212= (c.636A>G)?

DLX3 p.Ser212= (c.636A>G) is associated with hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (ClinVar).

How common is DLX3 p.Ser212= (c.636A>G) in the general population?

DLX3 p.Ser212= (c.636A>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

How is Amelogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DLX3 p.Ser212=

c.636A>G · rs759832786 · VCV888963

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.3	GERP -4.3
Overall
CADD	0.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/90,956 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00103% 15/1,461,610 alleles · ultra-rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLX3
Protein: p.Ser212=
Coding: c.636A>G
MANE Select: NM_005220
dbSNP: rs759832786
Type: single nucleotide variant
Location: chr17:49991745 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 1 PDB
Residue 212: the 'disordered' region

Full DLX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amelogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (United States)

Similar variants

DLX3 p.Asn282Lys Uncertain significance ★★ ⚠ same condition
DLX3 p.Gln47Arg Uncertain significance ★★ ⚠ same condition
DLX3 p.Pro233Leu Uncertain significance ★★ ⚠ same condition
DLX3 c.516+23C>T Benign ★★ same condition
DLX3 c.-134C>A Benign ★★ same condition
DLX3 c.-189G>T Benign ★★ same condition
DLX3 c.-64C>T Benign ★★ same condition
DLX3 c.*1016G>C Benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dlx3-p-ser212 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown